Synthetic oligonucleotides complementary to mRNA or double-stranded DNA, as a means to impair gene expression by either editing point mutations in genomic DNA or editing mRNAs, have provided the impetus to evaluate the therapeutic value of these macromolecules. In this regard, modified oligonucleotides carrying aminoalky phosphotriester functions have been prepared in an attempt to improve their binding affinity to complementary RNA targets which, eventually, may facilitate mRNA editing. This approach has led to the application of the aminobutyl group as a general phosphate protecting group in the synthesis of unmodified oligonucleotides,and a new method for the synthesis of stereospecific synthesis of modified oligonucleotides. These findings may bring mRNA editing, through the development of high affinity oligonucleotides, a step closer to exciting therapeutic and gene therapy applications. Improving the affinity of oligonucleotide analogues for complementary DNA and/or RNA targets may , in additon to modulate gene expression, lead to the development of sensitive diagnostic probes for the detection and quantification of, for example, ubiquitous viral contaminants in biologics regulated by CBER. Furthermore, oligonucleotide analogues have been found effective in the repair of point mutations in genomic DNA . Thus, the application of these oligonucleotides as vectors for gene therapy applications will soon be regulated by CBER. Consequently, knowledge in the synthesis of oligonucleotide analogues and the use of these biomolecules in either mRNA editing or gene therapy protocols would be useful in assessing delivery efficiency, safety, and efficacy of these vectors.